They all rock: A systematic comparison of conformational movements in LeuT-fold transporters

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Structure Pub Date : 2024-07-17 DOI:10.1016/j.str.2024.06.015

引用次数: 0

Abstract

Many membrane transporters share the LeuT fold—two five-helix repeats inverted across the membrane plane. Despite hundreds of structures, whether distinct conformational mechanisms are supported by the LeuT fold has not been systematically determined. After annotating published LeuT-fold structures, we analyzed distance difference matrices (DDMs) for nine proteins with multiple available conformations. We identified rigid bodies and relative movements of transmembrane helices (TMs) during distinct steps of the transport cycle. In all transporters, the bundle (first two TMs of each repeat) rotates relative to the hash (third and fourth TMs). Motions of the arms (fifth TM) to close or open the intracellular and outer vestibules are common, as is a TM1a swing, with notable variations in the opening-closing motions of the outer vestibule. Our analyses suggest that LeuT-fold transporters layer distinct motions on a common bundle-hash rock and demonstrate that systematic analyses can provide new insights into large structural datasets.

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它们都很震撼对LeuT折叠转运体构象移动的系统比较

许多膜转运体都具有 LeuT 折叠结构--两个五螺旋重复序列在膜平面上倒置。尽管有数以百计的结构，但尚未系统地确定 LeuT 折叠是否支持不同的构象机制。在对已发表的 LeuT 折叠结构进行注释后，我们分析了九种具有多种构象的蛋白质的距离差异矩阵（DDM）。我们确定了刚体和跨膜螺旋（TM）在转运循环不同步骤中的相对运动。在所有转运体中，膜束（每个重复的前两个 TM）相对于哈希（第三和第四个 TM）旋转。臂（第五个 TM）关闭或打开胞内前庭和外前庭的运动是常见的，TM1a 的摆动也是常见的，外前庭的开闭运动有明显的差异。我们的分析表明，LeuT-折叠转运体在共同的束链岩上层叠着不同的运动，并证明系统分析可以为大型结构数据集提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.